Cervical precancer and cancer risk by human papillomavirus status and cytologic interpretation: Implications for risk-based management

Background: Cervical cancer risks, estimated by using cervical intraepithelial neoplasia grade 3 (CIN3) or more severe diagnoses (>CIN3) endpoints, have not been quantified for different combinations of results from currently approved screening methods. Understanding these risks will guide optimal patient management. Methods:Women aged >25 years (n= 7,823) underwent highrisk human papillomavirus (hrHPV) and liquid-based cytology (LBC) testing. Women with hrHPV-positive results and/or abnormal LBC, plus a random subset of hrHPV and LBC negatives, underwent colposcopy; those without >CIN2 at baseline were screened annually by LBC and referred to colposcopy for an abnormal LBC (n = 7,392). One- and 3-year >CIN3 risks with 95% confidence intervals (95% CI) were calculated for paired hrHPV and LBC (hrHPV/LBC) results. Results: One-year >CIN3 risks ranged from 81.27% (95% CI, 66.02%-90.65%) for HPV16 positive/high-grade to 0.33% (95% CI, 0.18%-0.62%) for hrHPV negative/negative for intraepithelial lesion or malignancy (NILM). One-year >CIN3 risk for HPV16/NILM (13.95%; 95% CI, 10.98%-17.58%) was greater than low-grade squamous intraepithelial lesion (LSIL; 7.90%; 95% CI, 5.99%-10.37%; P = 0.002) and similar to hrHPVpositive/ LSIL (11.45%; 95% CI, 8.61%-15.07%; P = 0.3). Three-year >CIN3 risks for HPV16 positive/LSIL and HPV16/ atypical squamous cells of undetermined significance was 24.79% (95% CI, 16.44%-35.58%) and 24.36% (95% CI, 15.86%-35.50%), respectively, and 0.72% (95% CI, 0.45%-1.14%) for hrHPV negative/NILM. Conclusions: hrHPV and LBC results stratify cervical cancer risk by more than two orders of magnitude. HPV16-positive women, regardless of the LBC result, warrant immediate colposcopy. Women with concurrent HPV16 and high-grade LBC might consider treatment without a confirmatory biopsy with informed decision-making with their provider. Impact: These results provide relevant benchmarks for riskbased cervical cancer screening and management.